N-acetylcysteine in Liver Transplantation (NAC)
|The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.|
|ClinicalTrials.gov Identifier: NCT00736541|
Recruitment Status : Completed
First Posted : August 18, 2008
Last Update Posted : July 27, 2017
N-acetylcysteine (NAC) is used to treat Tylenol toxicity. NAC is a rich source of the sulfhydryl group (SH) which is important for replenishing the body's glutathione stores. Glutathione acts as a free radical scavenger, to decrease the damage that would be caused by those toxic radicals. Patients who undergo orthotopic liver transplantation (OLT) have a high incidence of post-operative renal dysfunction. The most common etiology of post-operative renal dysfunction is related to high levels of toxic free radicals. Free radicals may contribute to primary liver graft failure or delayed liver graft function.
Specific Aims & Objectives:
The primary objective of this study is to evaluate the efficacy of NAC in improving liver graft performance and lowering the incidence of post-operative renal dysfunction. The secondary objectives are to investigate the effect of NAC on endogenous glutathione body stores and its effect on FK506 induced toxicity.
|Condition or disease||Intervention/treatment||Phase|
|End Stage Liver Failure||Drug: N-acetylcysteine||Not Applicable|
This is a randomized, double-blind placebo-controlled study that investigates the use of NAC during and after OLT. A total of 100 patients will be recruited. Fifty will receive a placebo (normal saline) and the other fifty will receive NAC. The patients in the NAC group will receive a loading dose of 140 mg/kg IV of NAC over one hour at the start of the surgery. Thereafter, NAC will be repeated every 4 hours at a dose of 70 mg/kg IV, for a total of 13 doses. The placebo group will receive an equal volume of a normal saline infusion for 13 doses. Both groups will be followed for one year after their OLT. The following data will be recorded and collected: liver function tests, renal function tests, liver graft survival rate, patient survival, serum level of glutathione (GSH-PX/GR), duration of hospital and ICU stay. To evaluate the accuracy of calculated serum creatinine clearance (CSCC) in predicating the renal performance in OLT patients, another two serum markers will be estimated. The 1st one is Cystatin-C and the 2nd is Beta-trace. The data from CSCC, cystatin-C and beta-trace will be compared to find out which is the best marker in between these three tests to predicate the renal function. The data will be recorded daily for the first week after the surgery, then on days 14, 21, 30, 90, 180 and finely at the end of the first year after the OLT. Statistical analysis of the data will be performed at the conclusion of the study period to determine the difference in the outcome and morbidity and mortality between the two groups.
Objective and Specific Aims
- Assess the efficacy of NAC to preserve liver graft function and to improve patient/graft survival following orthotopic liver transplantation.
- Assess the efficacy of NAC to preserve kidney function in the patients undergoing OLT.
- Severity of the post reperfusion syndrome (PRS) will be compared in both groups by assessing hemodynamic parameters and the need for vasopressor support in the neohepatic stage.
- Liver graft function, the incidence of primary non-function and delayed function in both the treatment and placebo groups, will be assessed with post-operative liver function tests (ALT, AST, serum bilirubin, PT/INR, APTT, lactate, etc). Liver function tests will be assessed at one month, three month, six month and at one year following the OLT.
- The duration of ICU and hospital stays will be compared between the two groups.
- Survival rate (patient/graft) between the treatment and placebo groups will be compared at 1 month, 3 months, 6 months and 1 year.
- Renal function will be compared in the treatment and placebo groups by assessing the following parameters during and after liver transplantation: urine output (ml/24 hours), serum creatinine and BUN, calculated creatinine clearance.
- The incidence of postoperative acute renal failure (ARF) and the extent and duration of renal dysfunction will be compared between the treatment and the placebo groups.
- Investigating the effect of NAC on the endogenous glutathione peroxides/glutathione reductase (GSH-PX/GR) body stores in patients undergoing OLT.
- Investigating the effect of NAC on FK506 induced toxicity.
- Investigating the accuracy of two new markers for evaluating the renal function and glomerular filtration rate and compare them to CSCC.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||100 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)|
|Official Title:||Investigation of the Efficacy of N-acetylcysteine (NAC) to Protect Against Hepato-renal Ischemia-reperfusion Injury in Patients Undergoing Orthotopic Liver Transplantation|
|Study Start Date :||July 2004|
|Actual Primary Completion Date :||April 2007|
|Actual Study Completion Date :||January 2008|
The patients in the NAC group will receive a loading dose of 140 mg/kg IV of NAC over one hour at the start of the surgery. Thereafter, NAC will be repeated every 4 hours at a dose of 70 mg/kg IV, for a total of 13 doses
Other Name: NAC, GSH, cystatin-c, beta-trace
- improve patient and graft outcome. reduce the incidence of postoperative renal dysfunction [ Time Frame: one year ]
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00736541
|United States, Pennsylvania|
|Unversity of Pittsburgh Medical Center|
|Pittsburgh, Pennsylvania, United States, 15213|
|Principal Investigator:||Ibtesam A Hilmi, MB CHB, FRCA||University of Pittsburgh Medical Center|